The autologous mixed lymphocyte reaction represents the activation of T cells by self Ia molecules in the absence of conventional antigens. Although this reactivity has been described in rodents and humans, its relationship to self recognition required for immune reactivity occurring in vivo is not known. Utilizing autologous-reactive human T cell clones, autologous-reactive human T-T hybrids, a monoclonal antibody which appears to have specificity for the Ia receptor displayed by autologous reactive T cells, and a cDNA library established from an autologous reactive T cell hybrid, the following specific aims will be investigated: 1) determine the relationship between antigen reactive and autologous reactive T cells, 2) examine the ability of autologous reactive T cells to promote the differentiation of macrophages, 3) examine the effects of blocking the autologous mixed lymphocyte reaction, in vivo, on antigen reactivity, and 4) characterize the T cell receptor for self Ia with particular reference to determining structural and genetic polymorphism. These studies are not only important for establishing the significance of self recognition represented by the AMLR, but also for elucidating the nature of the T cell recognition unit for self Ia.